The objective in this study is to elucidate the basic mechanisms involved in the regulation of erythropoiesis and to apply this knowledge to human erythropoietic diseases. The techniques of marrow cell culture will be used to study the effect of erythropoietin (Ep) and endotoxin on marrow erythroid precursor cells. The effect of endotoxin on the number, state of cell cycle, velocity sedimentation at unit gravity and Ep sensitivity of murine day 3 and day 7 BFU-E will be determined. The relation of endotoxin, as a contaminant in most Ep preparations, to the development of day 7 BFU-E in vitro will be determined. These experiments should clarify the developmental characteristics and capacities of erythroid precursor cells by their response to endotoxin and Ep, and should aid in the interpretation of prior experiments up to this time that have been performed with contaminating endotoxin present in Ep preparations. The polycythemia produced by the Friend virus will also be studied. Friend virus markedly increases erythropoiesis in mice by a mechanism that does not require the presence of added Ep. We have shown that Friend virus produces erythroid bursts when added to mouse marrow cells in vitro. We will determine if the erythroid bursts produced by Friend virus in vitro are clones arising from a single cell by mixing male and female cells and determining if the bursts have a homogeneous karyotype. Studies will be performed to identify the in vitro target cells for Friend virus-induced erythroid bursts and to determine if Ep has a role in the production of erythroid bursts by the Friend virus in vitro. The relative roles of the spleen focus-forming virus and the murine leukemia virus complex will be investigated. The study of the effect of Friend virus on the early erythroid precursor cells will greatly increase our knowledge of the different developmental stages and capacities of these cells and should provide a model for neoplastic transformation in vitro. Finally, we will attempt to construct an animal model for polycythemia vera.